Pulmonary: Pathology Part II - COPDs Flashcards
1
Q
Volume effects of obstructive diseases?
A
- ↓ FCV – volume of air that can be forcefully expired is decreased
- ↓↓ FEV1 – volume of air forecfully expired during the first second is decreased
- ↓ FEV1/FCV – reduced ratio
- Total Lung Capacity (TLC) is usually Increased due to Air Trapping
2
Q
- Chronic productive cough, for > 3 months per year and not necessarily for over 2 years
- Highly a/w Smoking
- Hypertrophy of Bronchial Mucinous glands
- Wheezing, crackles, cyanosis (early onset hypoxemia due to shunting), Late-onset dyspnea, CO2retention
- Leads to ↑ thickness of Mucus glands relative to Bronchial wall thickness - small airways
- Reid index > 50%, Normal is < 40%
- Cyanosis ”Blue Bloater” – Mucus plugs
→ trap CO2 → ↑ PaCO2 → ↓ PaO2 → ↓ paO2 - ↑ Infection and ↑ Cor Pulmonale
A
Chronic Bronchitis
3
Q
- Destruction of Alveolar air sacs
- Loss of Elastic recoil and Collapse of airways during Exhalation results in obstruction and Air trapping
- Due to imbalance of Proteases and Antiproteases
- Inflammation → release of Proteases by neutrophils and macrophages
- a1 – antitrypsin (A1AT) neutralizes proteases
- Excessive inflammation or Lack of A1AT → destruction of Alveolar air sacs
-
Smoking is the most common cause of Emphysema
- Pollutants → excessive Inflammation and Protease-mediated damage
- Centriacinar emphysema → Severe in Upper Lobes
A
Mechanism of Emphysema
4
Q
- Lack of anti-protease leaves air sacs vulneralbe to protease-mediated damage → Panacinar Emphysema → Severe in Lower Lobes
-
Liver cirrhosis
- A1AT deficiency is due to misfolding of Mutated protein
- Mutant A1AT accumulated in ER of Hepatocytes → Liver damage
- Biopsy → Pink PAS-positive globules in Hepatocytes
A
A1AT deficiency
5
Q
Genetic severity of A1AT deficiency?
A
- PiM – normal allele → two copies are normally expressed (PiMM)
- PiZ – most common Clinically relevant mutation → results in significantly low levels of circulating A1AT
- PiMZ – heterozygotes are usually asymptomatic w/ ↓ circulating A1AT → significant risk for Emphysema w/ Smoking
- PiZZ – Homozygotes are significant for Panicinar emphysema and Cirrhosis
6
Q
Clinical features of Emphysema?
A
- Dyspnea and Cough w/ minimal sputum
- Prolonged expiration with Pursed lips (‘Pink-puffer’) to ↑ airway pressure prevent collapse
- Weight loss
- Increased AP diameter of chest (‘Barrel-chest’)
- Hypoxemia (due to destruction of Capillaries in the Alveolar sac) and Cor Pulmonale are Late Complications
7
Q
- Allergans induce TH2 phenotype in CD4+ T cells of genetically susceptible pts.
- TH2 cells secrete:
- IL-4 - mediates class switch to IgE
- IL-5 – attracts eosinophils
- IL-10 – stimulates TH2 cells and inhibits TH1 cells
-
Reexposure to allergen leads to IgE-mediated activation of Mast cells
- Release preformed Histamine granules
- Generation of Leukotrienes C4, D4, and E4 → Bronchoconstriction, Inflammation, and Edema (early-phase)
- Inflammation from protein derived from Eosinohils → damages cells and perpetuates Bronchoconstriction (late-phase)
A
Asthma Pathogenesis (Type I Hypersensitivity)
8
Q
Clinical features of Asthma?
A
-
Episodic and related to Allergan exposure
- Dyspnea, Cough, Wheezing, Tachypnea, Hypoxemia, ↓I/E ratio, Pulsus paradoxus, mucus plugging
- Productive cough w/ Spiral-shaped mucus plugs (Curschmann spirals epithelium forms mucus plugs) and Eosinophil-derived crystals (Charcot-Leyden crystals formed from breakdown of eosinophils in sputum)
- Severe, unrelenting attack → Status asthmaticus and Death
9
Q
Non-allergic causes of Asthma?
A
- Exercise
- Allergens
- Stress
- Viral infection, URIs
- Aspirin (AIA – aspirin intolerant asthma)
- Occupational exposures (dust, etc.)
10
Q
Mechanism of Bronchiectasis?
A
- Permanent dilation of Bronchioles and Bronchi
→ Loss of airway tone
→ results in Air trapping - Chronic necrotizing infection of bronchi
→ permanentrly dilated airways - Abnormal Chloride ion transport is a feature of Cystic fibrosis → widespread Bronchiectasis
- CFTR gene mutations lead to Cystic fibrosis and Widespread Bronchiectasis
11
Q
- Cystic fibrosis → thick secretions → mucus plugs → infection → damage
- Kartagener syndrome – inherited defect of the Dynein arm (Cilia), which is necessary for Ciliary movement, a/w Sinusitis, Infertility (poor mobility of sperm), and Situs inversus
- Tumor or Foreign body
- Necrotizing infection
- Allergic Bronchopulmonary aspergilosis – Hypersensitivity reaction to Aspergillus leads to Chronic inflammatory damage → pts. w/ Asthma and Cystic fibrosis
A
Causes of Necrotizing inflammation w/ Bronchiectasis?
12
Q
Clinical features of Bronchiectasis?
A
- Cough
- Dyspnea
- Foul-smelling purulent sputum
- Recurrent infections
- Hemoptysis
- Complications – Hypoxemia w/ Cor Pulmonale and Secondary (AA) Amyloidosis
13
Q
Two types of Emphysema?
A
- Centriacinar - associated with smoking
- Panacinar - associated with α1-antitrypsin deficiency
14
Q
How do you test Asthma?
A
Methacholine challenge
15
Q
A
Normal
16
Q
A
Obstructive
- Obstructive lung volume > normal
- ↑ TLC
- ↑ FRC
- ↑ RV
- In both Obstructive and Restrictive FEV1 and FVC are reduced
- FEV1 is more dramatically reduced in Obstructive
- ↓ FEV1 / FVC ratio
17
Q
A
Restrictive
- Restrictive lung volume < Normal
- In both Obstructive and Restrictive FEV1 and FVC are reduced
- FVC is more dramatically reduced in Restrictive
↑ FEV1 / FVC ratio
